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Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.
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Objective:To explore the predictive value of the serum C-reactive protein (CRP)/albumin (ALB) ratio (CAR) for organ damage in tsutsugamushi disease.Methods:The clinical data of 166 patients with tsutsugamushi disease admitted to the First Affiliated Hospital of Wenzhou Medical University from January 1, 2010 to December 31, 2020 were retrospectively analyzed. The patients were divided into the organ damage group (72 cases) and non-organ damage group (94 cases) according to the organ damage criteria. The general data and laboratory test results of the two groups of patients were compared. The significant indicators of univariate analysis were analyzed by multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of CAR for organ damage in patients with tsutsugamushi disease.Results:There were no significant differences in age, sex, days of fever, and admission body temperature between the organ damage group and non-organ damage group ( P>0.05). However, the body mass index, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), length of hospital stay, hospitalization expense, percentage of neutrophils (NEUT), lymphocyte count, procalcitonin, CRP, and CAR in the organ damage group were significantly higher than those in the non-organ damage group ( P<0.05), and ALB was significantly lower than that in the non-organ damage group ( P<0.05). Multivariate logistic regression analysis showed that APACHEⅡ( P=0.039), NEUT ( P=0.003), and CAR ( P=0.011) were independent risk factors for tsutsugamushi disease complicated by organ damage. The ROC curve showed that the AUCs of APACHEⅡ, NEUT, and CAR were 0.655, 0.716, and 0.727, respectively. When the cut-off value of CAR was 2.86, the sensitivity was 55.6%, and the specificity was 79.8%. Conclusions:Elevated CAR is an independent risk factor for tsutsugamushi disease complicated with organ damage and can be used as an important indicator to evaluate the presence or absence of organ damage in patients with tsutsugamushi disease.